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Backgrounds Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors. Methods and materials In this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling. Results The total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79–4.97), for both sexes, and 5.96 (5.82–6.10) for males, and 3.75 (3.64–3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01–1.13, p = 0.013 ), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33–1.60, p <  0.001 ), mothers with extreme obesity (OR = 1.32, 1.21–1.43, p <  0.001 ), mothers with grade II obesity (OR = 1.32, 1.23–1.42, p <  0.001 ), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04–1.31, p = 0.009 ), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71–2.25, p <  0.001 ), and mothers who used assisted reproductive technology (OR = 1.40, 1.18–1.66, p <  0.001 ). Conclusions Our findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Background: Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post-treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans. Methods: In this RCT, we assessed the safety of intraparenchymal injection placenta MSC-derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single-center as an open-label RCT, with a 3-months follow-up. Primary outcomes assessed the safety and also disability indexes were followed. Results: Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection. Conclusions: Intraparenchymal implantation of MSC-EXO showed no post-interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.

Production of a 3D bone construct with high-yield differentiated cells using an appropriate cell source provides a reliable strategy for different purposes such as therapeutic screening of the drugs. Although adult stem cells can be a good source, their application is limited due to invasive procedure of their isolation and low yield of differentiation. Patient-specific human-induced pluripotent stem cells (hiPSCs) can be an alternative due to their long-term self-renewal capacity and pluripotency after several passages, resolving the requirement of a large number of progenitor cells. In this study, a new biphasic 3D-printed collagen-coated HA/β-TCP scaffold was fabricated to provide a 3D environment for the cells. The fabricated scaffolds were characterized by the 3D laser scanning digital microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical test. Then, the osteogenesis potential of the hiPSC-seeded scaffolds was investigated compared to the buccal fat pad stem cell (BFPSC)-seeded scaffolds through in vitro and in vivo studies. In vitro results demonstrated up-regulated expressions of osteogenesis-related genes of RUNX2, ALP, BMP2, and COL1 compared to the BFPSC-seeded scaffolds. In vivo results on calvarial defects in the rats confirmed a higher bone formation in the hiPSC-seeded scaffolds compared to the BFPSC-seeded groups. The immunofluorescence assay also showed higher expression levels of collagen I and osteocalcin proteins in the hiPSC-seeded scaffolds. It can be concluded that using the hiPSC-seeded scaffolds can lead to a high yield of osteogenesis, and the hiPSCs can be used as a superior stem cell source compared to BFPSCs for bone-like construct bioengineering.

Adipose tissues hold great promise in bone tissue engineering since they are available in large quantities as a waste material. The buccal fat pad (BFP) is a specialized adipose tissue that is easy to harvest and contains a rich blood supply, and its harvesting causes low complications for patients. This review focuses on the characteristics and osteogenic capability of stem cells derived from BFP as a valuable cell source for bone tissue engineering. An electronic search was performed on all in vitro and in vivo studies that used stem cells from BFP for the purpose of bone tissue engineering from 2010 until 2016. This review was organized according to the PRISMA statement. Adipose-derived stem cells derived from BFP (BFPSCs) were compared with adipose tissues from other parts of the body (AdSCs). Moreover, the osteogenic capability of dedifferentiated fat cells (DFAT) derived from BFP (BFP-DFAT) has been reported in comparison with BFPSCs. BFP is an easily accessible source of stem cells that can be obtained via the oral cavity without injury to the external body surface. Comparing BFPSCs with AdSCs indicated similar cell yield, morphology, and multilineage differentiation. However, BFPSCs proliferate faster and are more prone to producing colonies than AdSCs.

Osteoporosis, a systemic skeletal disorder specified by low bone mass, is associated with bone fragility and the raised risk of fractures. Activation of the Wnt/β-catenin signaling pathway has been directly demonstrated as a prominent biological event in the prevention of osteoporosis. Recently, critical roles of microRNAs (miRNAs) were further revealed in Wnt/β-catenin signaling activation and thereby contributing to the development and maintenance of the human skeleton. In this study, we investigated whether miR-218 can significantly promote the osteogenic differentiation of mesenchymal stem cells in conditional media by regulating β-catenin signaling inhibitors. The pre-miRNA nucleotide sequence of miR-218 was cloned into the pEGP-miR vector. Next, human adipose tissue-derived mesenchymal stem cells (AD-MSCs) were isolated, characterized, and transfected using pEGP-miR-218.Subsequently, the osteogenic potential of AD-MSCs was investigated in different treated groups using alkaline phosphatase (ALP)activity, calcium mineral deposition, and the expression of osteogenesis-related genes. Finally, negative regulators of Wnt signaling targeted by miR-218 were bioinformatically predicted. Our results indicated a significant increase in the ALP activity, mineralization, and osteogenesis-related genes expression in the AD-MSCs transfected with pEGP-miR-218. Also, the bioinformatic surveys and gene expression results showed that adenomatosis polyposis coli (APC) and glycogen synthase kinase 3 (GSK3-β) were downregulated in the transfected AD-MSCs in both differential and conditional media. This study provided evidence that miR-218 can promote osteogenic differentiation of AD-MSCs even in conditional media. Therefore, our findings suggest miR-218 as a putative novel therapeutic candidate in the context of osteoporosis and other bone metabolism-related diseases.

Purpose The current systematic review investigated the results of application of some of the most commonly used scaffolds in conjugation with stem cells and growth factors in animal and clinical studies. Methods A comprehensive electronic search was conducted according to the PRISMA guidelines in NCBI PMC and PubMed from January 1970 to December 2015 limited to English language publications with available full texts. In vivo studies in relation to “bone healing,” “bone regeneration,” and at least one of the following items were investigated: allograft, β-tricalcium phosphate, deproteinized bovine bone mineral, hydroxyapetite/tricalcium phosphate, nanohydroxyapatite, and composite scaffolds. Results A total of 1252 articles were reviewed, and 46 articles completely fulfilled the inclusion criteria of this study. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used. Among studies being reported in this review, bone marrow mesenchymal stem cells are the most studied mesenchymal stem cells, β-tricalcium phosphate is the most frequently used scaffold, and platelet-rich plasma is the most commonly used growth factor. Conclusion The current review aimed to inform reconstructive surgeons of how combinations of various mesenchymal stem cells, scaffolds, and growth factors enhance bone regeneration. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used.

Objective(s): Exosomes, as nano-sized extracellular vehicles acting as cell-to-cell communicators, are novel promising therapeutics in the area of bone tissue engineering. Moreover, magnetic nanoparticles, whose integration with other appropriate components is viewed as an intriguing approach to strengthen bone tissue engineering efficacy. We investigated the effect of magnetic enriched with exosomes on osteogenic differentiation. Materials and Methods: Exosomes were isolated from human adipose-derived mesenchymal stem cells by Exo-spin™ kit (MSC-EX). Alginate (Alg) scaffold containing 1% (w/w) cobalt ferrite nanoparticles (CoFe2O4) was produced. MSC-EX were gently loaded onto Alg and Alg-cobalt ferrite (Alg-CF) scaffolds yielding Alg-EX and Alg-CF-EX scaffolds. The effects of MSC-Ex and magnetic hydrogel composite under an external static magnetic field (SMF) on proliferation and differentiation of MSCs were evaluated by alkaline phosphatase (ALP) activity measurement, alizarin red staining, and energy dispersive X-ray (EDX) analysis. Results: Our results showed that Alg and Alg-CF scaffolds were not only cytotoxic but also supported AdMSCs proliferation. MSC-EX loading of the scaffolds enhanced AdMSCs proliferation significantly. According to the results, Alg-CF-EX scaffolds under magnetic stimulation exhibited the most potent effect on osteogenic differentiation of cultured AdMSCs as evidenced by higher ALP activity and mineralization. Conclusion: We provided evidence that the combination of Alg hydrogel, CFNPs, and MSC-EX resulted in the construction of a bone tissue-engineering scaffold that highly supports the osteogenic commitment of MSCs.

Furthermore, the use of MA-T treatments outside of the living organism enhanced the formation of dentin matrix in developing tooth samples. [...]in vitro investigation shown that LiCl treatment increased the mRNA expression of Wnt10a and Wnt6 in odontoblasts, but had no effect on Wnt5a. In another study, Irfan et al. discovered that disabling the C5a-like receptor 2 (C5L2) CRISPR gene significantly improves the process of mineralization in TNFα-stimulated dental pulp stem cells (DPSCs), and promotes the production of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1. Present therapies mostly aim to alleviate symptoms and enhance quality of life, but do not restore impaired glands.

Bone tissue engineering necessitates the development of scaffolds with optimal properties to provide a suitable microenvironment for cell adhesion, proliferation, and osteogenic differentiation. The selection of appropriate scaffold materials remains a critical challenge in this field. In this study, we aimed to address this challenge by evaluating and comparing the performance of hydrogel scaffolds reinforced with β ‐tricalcium phosphate ( β ‐TCP), allograft, and a combination of allograft and strontium hydroxyapatite (SrHA). In this study, scaffolds containing the following compounds with a weight ratio of 75 : 25 : 50 were made using a 3D printer: group (1) alginate + gelatin +  β ‐TCP (TCP), group (2) alginate + gelatin + allograft (Allo), and group (3) alginate + gelatin + allograft + strontium hydroxyapatite (Str). Stem cells extracted from rat bone marrow (rBMSCs) were cultured on scaffolds, and cell proliferation and differentiation tests were performed. Also, the physical and chemical properties of the scaffolds were investigated. The two/one‐way analysis of variance (ANOVA) by Tukey’s post hoc test was performed. There was no significant difference between scaffolds with pore size and porosity. TCP scaffolds’ mechanical strength and degradation rate were significantly lower than the other two groups ( P < 0.05). Also, the swelling ratio of Allo scaffolds was higher than in other samples. The amount of cell proliferation in the samples of the TCP group was lower than the other two, and the Allo samples had the best results in this concern ( P < 0.01). However, the scaffolds containing strontium hydroxyapatite had significantly higher bone differentiation compared to the other two groups, and the lowest results were related to the scaffolds containing β ‐TCP. Hydrogel scaffolds reinforced with allograft or its combination with strontium showed better physicochemical and biological behavior compared to those reinforced with β ‐TCP. Besides, adding strontium had a limited impact on the physicochemical features of allograft‐containing scaffolds while improving their potential to induce osteogenic differentiation.